Cellular prion protein: implications in seizures and epilepsy |
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Authors: | Walz Roger Castro Rosa Maria R P S Velasco Tonicarlo R Carlotti Carlos G Sakamoto Américo C Brentani Ricardo R Martins Vilma R |
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Affiliation: | (1) CIREP, Center for Epilepsy Surgery, Ribeirão Preto School of Medicine, University Hospital, University of São Paulo, Ribeirão Preto, SP, Brazil;(2) Rua Prof. Antônio Prudente 109 4A, Ludwig Institute for Cancer Research, 01509-900 São Paulo, SP, Brazil;(3) Centro de Tratamento e Pesquisa Hospital do Câncer, São Paulo, SP, Brazil;(4) Laboratory of Molecular Biology, Surgery Department, Ribeirão Preto School of Medicine, University Hospital, University of São Paulo, Ribeirão Preto, SP, Brazil |
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Abstract: | 1. Cellular prion (PrPc) is a plasma membrane protein involved with copper uptake, protection against oxidative stress, cell adhesion, differentiation, signaling, and survival in the central nervous system2. Deletion of PrPc gene (Prnp) in mice enhances sensitivity to seizures in vivo and neuronal excitability in vitro which can be related to: (i) disrupted Ca+2-activated K+ currents, with loss of IHAP conductance in hippocampus; (ii) abnormal GABA-A inhibition in the hippocampus; (iii) mossy fiber reorganization in the hippocampus; (iv) changes in ectonucleotidases in both hippocampus and neocortex; and (v) higher levels of neocortical and subcortical oxidative stress. Moreover, postnatal Prnp knockout mice showed a significant reduction of after hyperpolarization potentials in hippocampal CA1 cells.3. Taken together, these findings suggest that loss of PrPc function contributes to the hyperexcitable and synchronized activities underlying epileptic seizures generated in neocortex and hippocampus. Hence, the role of PrPc on human symptomatic, cryptogenic or idiopathic epileptic syndromes deserves further investigation. |
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Keywords: | cellular prion protein neuroplasticity epileptogenesis seizures epilepsy |
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